A Multicenter Open-Label Randomized Phase II Study of Osimertinib With and Without Ramucirumab in Tyrosine Kinase Inhibitor-Naïve EGFR -Mutant Metastatic Non-Small Cell Lung Cancer (RAMOSE trial).

Autor:	Le X; UT MD Anderson Cancer Center, Houston, TX., Patel JD; Northwestern University, Chicago, IL., Shum E; New York University Cancer Center, New York, NY., Baik C; University of Washington, Seattle, WA., Sanborn RE; Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR., Shu CA; Columbia University Irving Medical Center, New York, NY., Kim C; Georgetown University, Washington, DC., Fidler MJ; Rush University, Chicago, IL., Hall R; Virginia University, Charlottesville, VA., Elamin YY; UT MD Anderson Cancer Center, Houston, TX., Tu J; UT MD Anderson Cancer Center, Houston, TX., Blumenschein G; UT MD Anderson Cancer Center, Houston, TX., Zhang J; UT MD Anderson Cancer Center, Houston, TX., Gibbons D; UT MD Anderson Cancer Center, Houston, TX., Gay C; UT MD Anderson Cancer Center, Houston, TX., Mohindra NA; Northwestern University, Chicago, IL., Chae Y; Northwestern University, Chicago, IL., Boumber Y; Northwestern University, Chicago, IL., Sabari J; New York University Cancer Center, New York, NY., Santana-Davila R; University of Washington, Seattle, WA., Rogosin S; Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR., Herzberg B; Columbia University Irving Medical Center, New York, NY., Creelan B; Moffitt Cancer Center, Tampa, FL., Pellini B; Moffitt Cancer Center, Tampa, FL., Tanvetyanon T; Moffitt Cancer Center, Tampa, FL., Heeke S; UT MD Anderson Cancer Center, Houston, TX., Hernandez M; UT MD Anderson Cancer Center, Houston, TX., Gray JE; Moffitt Cancer Center, Tampa, FL., Saltos A; Moffitt Cancer Center, Tampa, FL., Heymach JV; UT MD Anderson Cancer Center, Houston, TX.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2024 Oct 08, pp. JCO2400533. Date of Electronic Publication: 2024 Oct 08.
DOI:	10.1200/JCO.24.00533
Abstrakt:	Purpose: Preclinical studies demonstrated that dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways delay the emergence of resistance to EGFR tyrosine kinase inhibitors (TKIs), and in trials with first-generation EGFR TKIs, the combination of EGFR VEGF pathway inhibitors prolonged progression-free survival (PFS). Methods: The RAMOSE trial (ClinicalTrials.gov identifier: NCT03909334, HCRN LUN-18-335) is a randomized, open-label multicenter phase II study comparing osimertinib with ramucirumab (arm A) to osimertinib (arm B) for initial treatment of metastatic EGFR -mutant non-small cell lung cancer (NSCLC) with 2:1 random assignment. The primary end point is PFS for evaluable patients; secondary end points include objective response rates (ORRs), disease control rate (DCR), overall survival, and safety. The stratification criteria were EGFR mutation type and the presence of CNS metastasis. Results: At data cutoff on August 29, 2023, 160 patients consented, 147 patients received treatment, and 139 patients were evaluable with at least one scan. In this preplanned interim analysis, the median follow-up was 16.6 months. Among the evaluable patients, 57 PFS events occurred. The median PFS was 24.8 (A) versus 15.6 (B) months (hazard ratio, 0.55 [95% CI, 0.32 to 0.93]; log-rank P = .023), 12-month PFS rate was 76.7% (A) versus 61.9% (B; P = .026). No significant difference was observed in the ORRs and DCRs between arms. Any-grade (G) adverse events (AEs) occurred in 100% (A) and 98% (B) of patients, with no G5 treatment-related AE (TRAE), one G4 TRAE (hyponatremia, A), and 53% (A) versus 41% (B) G3 TRAEs. AE-related discontinuation occurred in 13 patients (9.7% in A and 8.7% in B). The safety profile was in line with known safety of each drug. Conclusion: Ramucirumab plus osimertinib significantly prolonged PFS compared with osimertinib alone in patients with TKI-naïve EGFR -mutant NSCLC. The combination is safe and well tolerated.
Databáze:	MEDLINE
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